The administration of gold thioglucose to experimental animals induces lesions in the ventromedial hypothalamus (VMH) which results in the production of hyperphagia and obesity. We have recently reported that in mice gold thioglucose induced hyperphagia and obesity was prevented by adrenalectomy and hypophysectomy, and restored by the administration of the adrenal corticoid, cortisone. Surprisingly, the mineralocorticoid, desoxycorticosterone, was found to suppress food intake of the VMH-lesioned adrenalectomized mice to such an extent that they could no longer maintain their body weight. In addition, we have found that if the VMH-lesioned mice were adrenalectomized after they have become grossly obese, all the mice exhibit a prolonged anorexia, loss in body weight, hypoglycemia and die within the course of a few weeks. This phenomenon is not seen in normal mice (with an intact VMH) following adrenalectomy. These findings establish a role of adrenal hormones in the regulation of food intake. The manner in which adrenal hormones interact, directly or indirectly, with components of the central nervous system involved in the control of feeding behavior is not well understood. We propose to determine whether adrenal hormones act directly on these components or indirectly, by altering the levels of other hormones and metabolic intermediates which in turn act on these structures.